Ultrafiltration membranes are being used widely by bio- and health-related research institutions as well as by biopharmaceutical industry for rapid size-based purification and separation of macromolecules, including proteins, nucleic acids and polysaccharides. Important medical applications include hemodialysis (treatment of end-stage renal failure) and open-heart surgery (blood oxygenation). In spite of the fact that a wide range of membranes with different specifications is available commercially, there is a strong need for improvement of membranes selectivity. The main approach to that is to narrow down pore size distribution, which is a challenge for the existing types of ultrafiltration membranes. This multi-phase Small Business Innovation Research project aims to develop and commercialize novel ultrafiltration membranes with unprecedented sharp and controllable molecular-weight cut-off and reduced fouling. Such membranes are needed to fully realize the potential benefits of ultrafiltration in the processing of macromolecules of biological and medical interest. The targeted product - novel membranes - will be suitable as drop-in replacements of the state-of-the- art membranes in commercial membrane holders. The proposed development will drastically improve rapid purification and separation of natural products in biochemical and medical research and in medical care applications and thus is directly relevant to the mission of the National Institute Of General Medical Sciences. The main Phase I objective is to demonstrate feasibility of the proposed approach by fabricating and testing ultrafiltration membranes and confirming their enhanced performance versus commercial analogs. To ensure successful Phase II product development and Phase III commercialization, an early partnership has been secured with a developer of low-cost non-invasive glucose sensors. PUBLIC HEALTH RELEVANCE: The project addresses a significant problem in biomedical research and medical care: rapid size-based purification and separation of macromolecules, including proteins, nucleic acids and polysaccharides. The development of novel advanced ultrafiltration membranes with unprecedented sharp and controllable molecular-weight cut-off and reduced fouling is proposed. The proposed technology will enable a novel family of high-performance membranes for use in biochemical analysis, laboratory studies, and, potentially, in hemodialysis for treatment of end-stage renal failure and in open heart surgery for blood oxygenation.